Berkeley - When early humans migrated to South America more than 10,000 years ago, they brought with them a deadly hitchhiker - the airborne fungus responsible for causing Valley Fever, a disease that has caused illness and death in hundreds of people in central California and throughout the Southwest. This spread of Valley Fever by people migrating to southern latitudes is being reported next week by University of California, Berkeley, researchers, who tracked the disease using genetic sleuthing of fungi cultivated from victims of the disease.

"We like to think of globalization of diseases as a modern event, but it has been taking place for tens of thousands of years," said John Taylor, a professor in the Plant & Microbial Biology Department in the UC Berkeley College of Natural Resources. With colleague Matthew Fisher, researchers at Roche Molecular Systems and four Latin American research institutions, Taylor published the research in the April 3 issue of Proceedings of the National Academy of Sciences (PNAS).

The discovery will help scientists learn more about the spread and evolution of the Valley Fever fungus, Coccidioides immitis, which grows in soils in hot, dry climates. Wind, farming and even landslides caused by earthquakes can stir up soil, causing fungal spores to become airborne and occasionally lodge in a susceptible person's lung. Within three weeks, the spores expand and burst to release more spores, causing symptoms such as fatigue, cough and chest pain. If untreated, death can result.

Recognized as a pathogen for just over a century, the C. immitis fungus kills about 50 people a year in North America. The disease affects approximately 100,000 people per year, although most never know they've been infected. Periodic epidemics, like one that occurred in the early 1990s in Bakersfield, Calif., may be triggered by climatic events like drought. "Climate change and human disease are intricately related," said Taylor. "It is a phenomenon we will see more of as we continue to experience global warming."

To study the historical migration of the fungus, the researchers assembled 161 fungal isolates from patients who had visited health clinics throughout the affected region - Central and Southern California, Arizona, Texas, Central and Southern Mexico and South America. In addition, they studied two samples collected from environmental sources, one from the soil and another from an armadillo.

From each fungus, the researchers isolated DNA and then selected certain regions of the genome called microsatellites, which are short repeating bits of DNA. Using similarities in the DNA code of each microsatellite, the researchers grouped the fungi into eight distinct groups, each from a different geographical region. These eight groups all originated from a common ancestor, but became genetically distinct populations through genetic isolation and natural mutations.

The researchers noticed something curious. Two of the populations, one collected in Texas and the other in South America, were very similar. Previous work indicated that the ancestral fungus had occupied California and Arizona, so the researchers knew the fungus must have migrated south rather than north. "This led us to conclude that the fungus moved into South America recently and has not had time to display genetic changes," said Taylor.

Further analysis of how the DNA sequence diverged over time led the researchers to determine that the fungus reached South America between 9,000 and 140,000 years ago, which coincides with archeological evidence of the arrival of Homo sapiens to the region.

The fungal spores were probably carried as tiny spheres lodged in the lungs of domesticated animals or infected humans, who can carry latent C. immitis spores for up to 12 years. The fungus has been found in Native American middens in North America, showing that the disease was prevalent amongst these people.

Although the migration southward occurred thousands of years ago, Taylor said the disease is still capable of being carried around the globe. "Humans can contract the disease in California or Arizona and carry it to unexposed parts of the world," said Taylor. "However, even if those areas were dry enough to support the fungus, it would be unlikely to spread."

The fungus cannot spread directly from human to human. To complete its life cycle, C. immitis must make spores in the soil, where it migrates by seeping into soil from an infected animal's corpse. "Modern human burial practices prevent this from happening with people, but not so 12,000 years ago," said Taylor.

When in the "soil spore stage," C. immitis is quite infective and as a result it is the only fungus on the list of terrorist organisms under the U.S. Effective Death Penalty and Anti-Terrorism Act, said Taylor.

This work was supported by grants from the National Institutes of Health and UC Berkeley's Miller Institute for Basic Research in Science.